Browsing by Author "Sadhabiriss, Dhiren."

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Outpatient treatment of drug-resistant tuberculosis in a hyperendemic setting.
(2021) Pillay, Jashen.; Gounden, Strinivasen.; Sadhabiriss, Dhiren.; Magula, Nombulelo Princess.
Background: The existence of multidrug-resistant tuberculosis (MDR-TB) represents a failure of effective infection control. There are over half a million new cases diagnosed annually with treatment success rates of only 57% reported in 2019. These numbers are highest in hyperendemic regions of the world, including South Africa, which has a high burden of tuberculosis and HIV co-infection. Treatment of MDR-TB is challenging and is usually managed at specialised centres. There is currently a transition into the decentralised treatment of MDR-TB for outpatients. Describing the features of DR-TB may influence improved treatment strategies for the future. Objectives: To determine the prevalence of DR-TB at a single, central outpatient site in a hyperendemic area of South Africa, and to evaluate known risk factors and their relationship with outcomes, including time between diagnosis and treatment initiation. Methods: A retrospective chart review of all new cases of DR-TB referred to a central hospital in Durban for outpatient care for the period 01/01/2017 to 31/03/2017 was conducted. Data included demographics, co-morbidities, time-to-treatment, treatment adverse effects and outcomes and were collected and collated from physical charts and the computerised registry. The data was then analysed using SPSS software. Results: The period prevalence of MDR-TB at the site was 44 cases/100 000 population. Of these cases, one hundred and eleven new cases of DR-TB were included in the analysis which comprised 57 (51.35%) males. Most patients were of African ethnicity (n = 107, 96.4%). Thirty-one (27.9%) patients did not have HIV co-infection. More than one-half of patients (n = 56, 51.5%) had a history of TB and was significantly higher in males than in females (n = 34, 59.6%) and n = 22, 40.7%) respectively; p= 0.020). Five (4.5%) patients had co-morbidities of hypertension, diabetes mellitus, or renal impairment. Most patients (n = 98, 88.3%) were treated within three months of diagnosis. The mean time-to-treatment was significantly longer in patients with extrapulmonary DR-TB (150.14 (±175.90) days compared to 53.21 (±66.01) days; p-value=0.002). Significantly more patients were treated within 6 weeks if they had a positive GeneXpert test (n = 35, 89.7% compared to n = 11, 17.5%, p=0.013). Fifty-one different treatment regimens were used, and 139 side-effects were reported, the most common being ototoxicity, hypothyroidism and peripheral neuropathy. Eighty-two (73.87%) patients completed follow-up until cure. Conclusion: The high burden of TB and HIV co-infection as well as a history of TB are associated with the elevated prevalence of MDR-TB in this setting. Side-effects are common and may impact toward poorer treatment adherence in addition to co-morbidities. Outcomes are favourable in specialised outpatient settings. A decentralised approach reduces the time-to-treatment in other studies, but large-scale implementation is recommended for further evaluation.
Tenofovir microbicide gel as an effective prophylactic measure to human herpes virus-8.
(2019) Bhorat, Raeesa Ismail.; Kharsany, Ayesha Bibi Mahomed.; Sadhabiriss, Dhiren.
Background: High prevalence and incidence rates of human herpes virus-8 (HHV-8) contributes significantly in the aetiology of cancers, including Kaposi sarcoma (KS). These cancers remain among leading causes of morbidity and mortality especially in people who are immunocompromised. Aim: To determine the effectiveness of 1% topical tenofovir disoproxil fumarate (TDF) as a vaginal gel formulation on HHV-8 acquisition amongst participants enrolled in the CAPRISA 004 trial. Methods: The CAPRISA 004 trial was a randomised controlled trial which investigated the effect of TDF gel on Human immunodeficiency virus (HIV) acquisition. A total 889 women from urban and rural settings in KwaZulu-Natal, aged 18 to 40 years were enrolled in the study and the samples from these women were tested for HHV-8 infections. Peripheral blood samples collected at enrolment and at the study exit visit were tested with Biotrin’s indirect immunofluorescent system to measure antibody to HHV-8 lytic antigens. HHV-8 prevalence was evaluated by sociodemographic factors and incidence by study arm and location. Descriptive statistics included means and standard deviation for quantitative data and frequencies for categorical data with Fisher’s exact test. Poisson regression was used to evaluate the incidence rate. A two-tailed p-value of less than 0.05 was considered significant in hypothesis testing and 95% confidence intervals (95% CI) are reported. Results: At baseline testing, 54 of 889 participants were HHV-8 positive with a prevalence of 6.12%. A higher parity (p=0.014) and higher number of sexual partners (p<0.001) as well as a rural setting (p=0.014) were associated with higher prevalence. With 40 infections among the 660 participants, the overall HHV-8 incidence rate was 3.98 per 100 person-years (PY) (95% Confidence Interval [CI] 2.84-5.42). Twenty infections occurred among participants assigned to the TDF arm with an HHV-8 incidence rate of 4.05 per 100 PY (95% CI 2.48-6.26) compared to the 20 infections among participants assigned to the placebo arm with an HHV-8 incidence rate of 3.91 per 100 PY (95% CI 2.39-6.04) (Incidence rate ratio (IRR) of 1.04, 95% CI 0.56-1.93; p=0.909). There were no differences in the HHV-8 incidence rates among participants assigned to the TDF and placebo arms in rural (IRR 1.40, 95% CI 0.66-2.95), p=0.383 or urban settings (IRR.51, 95% CI 0.15-1.68), p=0.266. HIV incidence rate among participants with prevalent HHV-8 infections was 6.48 per 100 PY (95% CI 2.11-15.13) and was similar to the HIV incidence rate of 7.35 per 100 PY (95% CI 5.92-9.01) among participants who remained HHV-8 negative, IRR of 0.88 (95% CI 0.36-2.17), p=0.785. Conclusion: The study showed that among women in rural and urban settings in KwaZulu-Natal, South Africa, the prevalence of HHV-8 infection was high and that TDF was not effective in the prevention of HHV-8 infection.
Tenofovir microbicide gel as an effective prophylactic measure to human herpes virus-8.
(2019) Raeesa., Ismail Bhorat.; Kharsany, Ayesha Bibi Mahomed.; Sadhabiriss, Dhiren.
Background: High prevalence and incidence rates of human herpes virus-8 (HHV-8) contributes significantly in the aetiology of cancers, including Kaposi sarcoma (KS). These cancers remain among leading causes of morbidity and mortality especially in people who are immunocompromised. Aim: To determine the effectiveness of 1% topical tenofovir disoproxil fumarate (TDF) as a vaginal gel formulation on HHV-8 acquisition amongst participants enrolled in the CAPRISA 004 trial. Methods: The CAPRISA 004 trial was a randomised controlled trial which investigated the effect of TDF gel on Human immunodeficiency virus (HIV) acquisition. A total 889 women from urban and rural settings in KwaZulu-Natal, aged 18 to 40 years were enrolled in the study and the samples from these women were tested for HHV-8 infections. Peripheral blood samples collected at enrolment and at the study exit visit were tested with Biotrin’s indirect immunofluorescent system to measure antibody to HHV-8 lytic antigens. HHV-8 prevalence was evaluated by sociodemographic factors and incidence by study arm and location. Descriptive statistics included means and standard deviation for quantitative data and frequencies for categorical data with Fisher’s exact test. Poisson regression was used to evaluate the incidence rate. A two-tailed p-value of less than 0.05 was considered significant in hypothesis testing and 95% confidence intervals (95% CI) are reported. Results: At baseline testing, 54 of 889 participants were HHV-8 positive with a prevalence of 6.12%. A higher parity (p=0.014) and higher number of sexual partners (p<0.001) as well as a rural setting (p=0.014) were associated with higher prevalence. With 40 infections among the 660 participants, the overall HHV-8 incidence rate was 3.98 per 100 person-years (PY) (95% Confidence Interval [CI] 2.84-5.42). Twenty infections occurred among participants assigned to the TDF arm with an HHV-8 incidence rate of 4.05 per 100 PY (95% CI 2.48-6.26) compared to the 20 infections among participants assigned to the placebo arm with an HHV-8 incidence rate of 3.91 per 100 PY (95% CI 2.39-6.04) (Incidence rate ratio (IRR) of 1.04, 95% CI 0.56-1.93; p=0.909). There were no differences in the HHV-8 incidence rates among participants assigned to the TDF and placebo arms in rural (IRR 1.40, 95% CI 0.66-2.95), p=0.383 or urban settings (IRR.51, 95% CI 0.15-1.68), p=0.266. HIV incidence rate among participants with prevalent HHV-8 infections was 6.48 per 100 PY (95% CI 2.11-15.13) and was similar to the HIV incidence rate of 7.35 per 100 PY (95% CI 5.92-9.01) among participants who remained HHV-8 negative, IRR of 0.88 (95% CI 0.36-2.17), p=0.785. Conclusion: The study showed that among women in rural and urban settings in KwaZulu-Natal, South Africa, the prevalence of HHV-8 infection was high and that TDF was not effective in the prevention of HHV-8 infection.
Warfarin: time in therapeutic range, a single centre study on patients using warfarin for stroke prevention in non-valvular atrial fibrillation and prosthetic heart valves.
(2016) Sadhabiriss, Dhiren.; Brown, Susan Lynn.
Background: There are various indications for the use of oral anticoagulants. Two common indications are in patients with atrial fibrillation and prosthetic heart valves. The quality of anticoagulation, determined by the time in therapeutic range, is less often evaluated and has important clinical implications in patient outcomes. Objectives: We sought to identify the indications for anticoagulation and determine the time in therapeutic range and the time out of range at a community-based and district level in patients attending the outpatient department at Mahatma Gandhi Memorial Hospital in KwaZulu Natal, South Africa. Further, we identified factors associated with the quality of anticoagulation and identified prevalence and contributors to thrombo-embolic and haemorrhagic events in anticoagulated patients with atrial fibrillation and prosthetic heart valves. Overview of thesis: Chapter 1 is a review of the literature and identifies the objectives of the study. Chapter 2 describes the study design and methodology. The sample population is described in Chapter 3. Chapter 4 and 5 evaluates the time in therapeutic range and Chapter 6 evaluates for associations thereof. Chapter 7 describes the findings of adverse events and the final chapter summarises the thesis with a general discussion and conclusion. Methods: We conducted a retrospective, descriptive and observational study with chart audits evaluating the anticoagulation control for the preceding one year for each patient. Descriptive statistics included mean and standard deviation for quantitative data and frequencies for categorical data. The variables demonstrated uniformity with linear plots and therefore comparisons of means was conducted by parametric testing. Analysis of variance was conducted for comparisons of variables with post hoc analysis for three groups. Confidence intervals were reported as 95%. Two-tailed p-values were conducted and any p-value less than .05 was considered significant. Results: TTR was poor for patients with atrial fibrillation and prosthetic valves (44.5% and 13.7% respectively). We identified older age, less frequent testing and high target ranges as significant factors associated with poorer outcomes. We demonstrated a high prevalence of adverse events (25.4%). Conclusion: Patients in this setting demonstrated poor quality of anticoagulation and had a high prevalence of adverse events.